| Project/Area Number |
15K21057
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pharmacology in pharmacy
Medical pharmacy
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| Research Institution | Nagoya University |
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Principal Investigator |
ODA Shingo 名古屋大学, 医学系研究科, 特任助教 (10725534)
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| Research Collaborator |
SHIRAI Yuji 名古屋大学, 大学院医学系研究科, 大学院生
XU Jieyu 名古屋大学, 大学院医学系研究科, 大学院生
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 薬物性肝障害 / 薬物代謝 / in vitroアッセイ / 免疫 / 炎症 / 肝障害 / 炎症反応 / 細胞アッセイ / 薬剤性肝障害 / DILI / in vitro / HepaRG / 予測試験系 |
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| Outline of Final Research Achievements |
This study sought to develop a novel cell-based assay for detecting potential drug-induced liver injury (DILI) by considering drug metabolism as well as immune- and inflammatory-related factors. Human hepatoma HepaRG or HepG2 cells were treated with drugs with different clinical DILI risks. The conditioned media were subsequently used to treat human promyelocytic leukemia HL-60 cells, and the mRNA expression levels were measured. ROC-AUC was calculated to evaluate the predictive performance of each gene mRNA as a marker to assess DILI risk. The expression of IL-8 in HL-60 cells treated with conditioned media from HepaRG cells (HL-60/HepaRG) exhibited the highest ROC-AUC value of 0.758. An integrated score calculated from the levels of S100A9, IL-1beta, and IL-8 more precisely determined the DILI risks than individual gene expression did. The developed cell-based assay using immune-related gene expression would be useful for the detection of potential DILI risks.
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